Pre-formulation Development

Physical & Chemical Stability

Accelerated stressing stability studies are performed in SARA Pharm Solutions’ labs in accordance to the ICH guidelines. These studies are tailored to meet customer requirements.

Through such an investigation, the risks of scaling-up a formulation, which is not physically or chemically stable, are brought to zero.

In addition, we assess formulated drug stability up to 3-6 months or longer by using advanced solid-state characterization techniques (e.g., HT-XRPD, HR-XRPD, PLM, DSC, TGA, IR, Raman, HPLC, NMR etc).

Solubility Determination and Dissolution Profile

SARA Pharm Solutions scientists carry out quantitative thermodynamic solubility determinations in pure water, buffers, and water/co-solvents mixtures.
Quantitative assessment of solubility is easily performed using HPLC, in bio-relevant media such as Fasted State Simulated Gastric Fluid, Fasted or Fed State Simulated Intestinal Fluids (FaSSGF, FaSSIF or FeSSIF).
Solubility accurate evaluation is part of our integrated pre-formulation package where pharmaceutically acceptable excipients are used or during the screening programs if the customer requests the aqueous solubility determination of the tested API.

Deliquescence vs. Hygroscopicity Investigation

In order to study if the changes in the moisture level of API can influence chemical stability, flowability and compressibility, API is stored in different conditions of temperature and humidity (e.g., at 25°C/80%RH). The phase changes are investigated by Dynamic Vapor Sorption (DVS), coulometric Karl Fisher (cKF), TGA/DSC and XRPD.

The investigation of solid forms behavior under other controlled conditions (0-90%RH, and temperature) is made using a Dynamic Vapor Sorption instrument. As a result of this investigation SARA Pharm Solutions scientists assess the developability of each solid form.
The DVS data are correlated to the physico-chemical stability of the drug that have a great impact on selection of:

  • drug storage conditions
  • drug protection/stabilizing/formulation agents
  • final drug product packaging

Processes like hydration, polymorphic transformation/ re-crystallization and crystallization of amorphous are investigated using the the XRPD or TGA/DSC techniques after DVS analysis.

Excipient Compatibility

Chemistry of drug-excipient interaction constitutes a well-defined service package.
We screen a large variety of excipients. This may include lactose, microcrystalline cellulose, cicrocrystalline cellolose and cellulose derivatives (HPC, HPMC, etc.), starch and starch derivatives, stearic acid, and many others.
We focus on the following aspects:

  • change in color or physical appearance
  • change of polymorphic form
  • variation in dissolution rate or solubility

We make use of all the advanced solid-state techniques to assess the drug-excipient compatibility ensuring the success of drug formulation.